Functional Characterization of Gene Regulatory Elements

Abstract

Nucleotide variation in gene regulatory elements is a major determinant of phenotypes including morphological diversity between species, human variation and human disease. Despite continual progress in the cataloging of these elements, little is known about the code and grammatical rules that govern their function. Deciphering the code and their grammatical rules will enable high‐resolution mapping of regulatory elements, accurate interpretation of nucleotide variation within them and the design of sequences that can deliver molecules for therapeutic purposes. To this end, we are using massively parallel reporter assays (MPRAs) to simultaneously test the activity of thousands of gene regulatory elements in parallel. By designing MPRAs to learn regulatory grammar or to carry out saturation mutagenesis of every possible nucleotide change in disease causing gene regulatory elements, we are increasing our understanding of the phenotypic consequences of gene regulatory mutations. To better understand how nucleotide changes in gene regulatory elements lead to morphological differences between species, we are using the developing bat wing as a model. Using a combination of whole‐genome sequencing, RNA‐seq and ChIP‐seq (H3K27ac, H3K27me3) on developing bat and mouse forelimbs and hindlimbs at three sequential embryonic stages, we are attempting to decipher the molecular events that underlie bat wing development.Support or Funding InformationNICHD, NCI, NHGRI, NIMH, NHLBIThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.